调控METTL3表达对子宫内膜癌细胞增殖、凋亡的影响及机制研究

Effects and mechanisms of regulating METTL3 expression on proliferation and apoptosis of endometrial cancer cells

目的 探究靶向调控甲基转移样酶3(methyltransferase like 3,METTL3)表达对子宫内膜癌细胞增殖、凋亡的影响及相关作用机制。方法 选取子宫内膜癌细胞,经培养后分为对照组、过表达METTL3组、沉默METTL3组,三组细胞分别干预。对三组细胞增殖、凋亡、侵袭、迁移能力、METTL3、磷酸化细胞外信号调节激酶(p-ERK)、Wnt3a、β-连环蛋白(β-catenin)、微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)、哺乳动物ATG6同源蛋白(Beclin-1)、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、基质金属蛋白酶-9(MMP-9)相对表达量进行检测。结果 沉默METTL3组细胞METTL3、p-ERK表达、增殖率、Wnt3a、β-catenin表达、细胞侵袭细胞数、迁移细胞数、PI3K、Akt、MMP-9表达均低于对照组、过表达METTL3组(P <0.05);细胞凋亡率、LC3-Ⅱ、Beclin-1表达高于对照组、过表达METTL3组(P <0.05)。结论 沉默METTL3表达使凋亡、自噬、侵袭相关蛋白表达受到调控,从而影响子宫内膜癌细胞生物学行为。

Objective To explore the effect of targeted regulation of methyltransferase like 3(METTL3) expression on the proliferation and apoptosis of endometrial cancer cells and the related mechanisms.Methods Endometrial cancer cells were selected and cultured and divided into control group,METTL3 overexpression group,and METTL3 silenced group.The cells of the three groups were intervened respectively.The following index were tested:proliferation,apoptosis,invasion,migration ability of the cells in each groups,METTL3,phosphorylated extracellular signal-regulated kinase(p-ERK),Wnt3a,β-catenin(β-catenin),microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ),mammalian ATG6 homologous protein(Beclin-1),phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),matrix metalloproteinase-9(MMP-9) relative expression.Results The expression of METTL3,p-ERK,proliferation rate,Wnt3a,β-catenin expression,number of invasive cells,number of migrating cells,PI3K,Akt and MMP-9 expression in METTL3 silence group were lower than those in control group and METTL3 overexpression group.The mortality,LC3-Ⅱ and Beclin-1 expression were higher than those in the control group and METTL3 overexpression group(P<0.05).Conclusion Silencing METTL3 expression regulates the expression of apoptosis,autophagy,and invasionrelated proteins,thereby affecting the biological behavior of endometrial cancer cells.